Balloon angioplasty has been used for the treatment of narrowed and occluded blood vessels. A frequent complication associated with the procedure is restenosis, or vessel re-narrowing. Within 3 to 6 months of angioplasty, restenosis occurs in almost 50 percent of patients. To reduce the incidence of re-narrowing, several strategies have been developed. Implantable devices, such as stents, have been used to reduce the rate of angioplasty-related restenosis by about half. The use of such intraluminal devices has greatly improved the prognosis of these patients. Nevertheless, restenosis remains a formidable problem associated with the treatment of narrowed blood vessels.
Restenosis associated with interventional procedures such as balloon angioplasty may occur by at least two mechanisms: thrombosis and intimal hyperplasia. During angioplasty, a balloon is inflated within an affected vessel, thereby compressing the blockage and imparting a significant force, and subsequent trauma, upon the vessel wall. The natural antithrombogenic lining of the vessel lumen may become damaged, thereby exposing thrombogenic cellular components, such as matrix proteins. The cellular components, along with the generally antithrombogenic nature of any implanted materials (e.g., a stent), may lead to the formation of a thrombus, or blood clot. The risk of thrombosis is generally greatest immediately after the angioplasty.
A second mechanism of restenosis is intimal hyperplasia, or excessive tissue re-growth. The trauma imparted upon the vessel wall from the angioplasty is generally believed to be an important factor contributing to hyperplasia. This exuberant cellular growth may lead to vessel “scarring” and significant restenosis. The risk of hyperplasia-associated restenosis is usually greatest 3 to 6 months after the procedure.
Prosthetic devices, such as stents or grafts, may be implanted during interventional procedures such as balloon angioplasty to reduce the incidence of vessel restenosis. To improve device effectiveness, stents may be coated with one or more therapeutic agents providing a mode of localized drug delivery. The therapeutic agents are typically intended to limit or prevent the aforementioned mechanisms of restenosis. For example, antithrombogenic agents such as heparin or clotting cascade IIb/IIIa inhibitors (e.g., abciximab and eptifibatide) may be coated on the stent, thereby diminishing thrombus formation. Such agents may effectively limit clot formation at or near the implanted device. Some antithrombogenic agents, however, may not be effective against intimal hyperplasia. Therefore, the stent may also be coated with antiproliferative agents or other compounds to reduce excessive endothelial re-growth. Therapeutic agents provided as coating layers on implantable medical devices may effectively limit restenosis and reduce the need for repeated treatments.
Several strategies have been developed for coating one or more therapeutic agents onto the stent surface. Standard methods may include dip coating, spray coating, and chemical bonding. The therapeutic agent coating may be applied as a mixture, solution, or suspension of polymeric material and/or drugs dispersed in an organic vehicle or a solution or partial solution. Further, the coating may include one or more sequentially applied, relatively thin layers deposited in a relatively rapid sequence. The stent is typically in a radially expanded state during the application process. In some applications, the coating may include a composite initial tie coat, or undercoat, and a composite topcoat, or cap coat. The coating thickness ratio of the topcoat to the undercoat may vary with the desired effect and/or the elution system. Examples of various stent coating strategies are discussed in the background portion of U.S. Pat. No. 6,517,889 issued to Jayaraman.
Regardless of the strategy used to coat the stent, the coating material is generally deposited directly on the stent framework and joints. The material, especially when it is thicker, may serve to “stiffen” the stent structure. As such, the stent may not easily be able to move (e.g., bend and flex) when deployed within the vasculature. In some instances, problems may arise when the “stiffened” stent is deployed in a mobile vascular site (e.g., arm, leg, neck, etc.). The vascular endothelium may even sustain damage should the coated stent not move in compliance with the vessel. This may negate the beneficial effects of the coating and the stent itself. Therefore, it would be desirable to provide a strategy for delivering a therapeutic agent associated with a stent that would not restrain the movement of the stent.
Another shortcoming associated with some coated stents relates to the generally complex and time-consuming coating/layering process. The use of multiple layers and various coating geographies (i.e., coatings differentially positioned on the stent) may be expensive, time-consuming, and inefficient due to the elaborate coating machinery, step number, and complexity sometimes involved. The process may be further complicated for stent coatings including multiple drugs, polymers, and solvents, some of which may be immiscible and/or incompatible with one another. As such, it would be desirable to provide a relatively inexpensive and efficient strategy for delivering one or more therapeutic agents on a stent.
Yet another shortcoming associated with some coated stents relates to drug load. Many stents are constructed from a thin mesh framework and thus do not include a sufficiently large surface area to retain substantial amounts of therapeutic agent(s). Therefore, it would be desirable to provide a strategy for increasing the amount of therapeutic agent(s) carried by the stent.
Accordingly, it would be desirable to provide an intraluminal stent including therapeutic agent delivery pads, and a method of manufacturing the same, that would overcome the aforementioned and other disadvantages.